Significance of CD 105 expression for tumour angiogenesis and prognosis in endometrial carcinomas.
ABSTRACT Angiogenesis is a key process in tumour growth and metastasis, and Factor-VIII microvascular density has been found to influence prognosis among endometrial carcinoma patients. The CD105/endoglin antibody has been reported to preferentially bind to activated endothelial cells in tissues participating in angiogenesis, and we therefore wanted to compare the prognostic significance of CD105/endoglin to that of Factor-VIII. In a population-based endometrial carcinoma study with long (median 11.5 years) and complete patient follow-up, mean intratumour microvascular density (MVD) assessed using CD105/endoglin was investigated and compared with previous data for MVD assessed using Factor-VIII. MVD by CD105/endoglin was significantly correlated with MVD by Factor-VIII (p=0.001). However, tumours within the two groups defined by the upper and lower quartiles for CD105/endoglin-MVD were both significantly more often metastatic (FIGO-stage III/IV; p=0.03), with high tumour cell proliferation by Ki67 (p=0.007) and with reduced survival (p=0.036) as compared with the intermediate groups. In Cox regression analysis, CD105/endoglin-MVD showed independent prognostic influence when analysed together with patient age, FIGO stage, histologic subtype, histologic grade and Factor-VIII-MVD, while the latter lost its prognostic impact when CD105/endoglin was included. In the subgroup with high MVD, there was a tendency towards improved response to radiation therapy. In conclusion, CD105/endoglin-MVD is significantly associated with FIGO stage, tumour proliferation and prognosis in endometrial carcinoma, indicating that this is a better angiogenic marker in these tumours.
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ABSTRACT: The relationship between neovasculature in hepatocellular carcinoma (HCC) and the prognosis of patients still remains controversial. The aim of the present study was to investigate the prognostic significance of morphologic features of the microvessels in patients with HCC after resection. The paraffin-embedding specimens of 98 consecutive HCC patients, who received primary resection between 2000 and 2002, were collected from our prospective established tumor bank. The intratumoral microvessels were evaluated by immunohistochemical staining for CD31 and CD34. The disease-free survival (DFS) and overall survival (OS) of patients were analyzed by Kaplan-Meier analysis and Cox proportional hazards regression model. There are two distinct microvessel types: capillary-like and sinusoid-like were identified in tumor tissues. The patients could be divided into two groups according to their microvessel types. Both DFS and OS of capillary group patients (n = 65) were better than those of sinusoid group patients (n = 33). Multivariate analyses showed that the microvessel type was an independent risk factor for DFS (P = 0.016) and OS (P = 0.004) of this cohort. Capillary-like microvessels were more common in small HCC, and were significantly associated with higher microvessel density, while sinusoid-like microvessels were significantly correlated with lower microvessel density. The results of our study suggested that the microvessel type is an effective predictor of survival in patients with HCC after resection, which might serve as potential novel therapeutic targets for prevention of the recurrence of HCC after resection.Journal of Gastroenterology and Hepatology 05/2011; 26(5):866-74. · 3.33 Impact Factor
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ABSTRACT: The aims of this study are (1) to evaluate the spatial distribution of neovessels and mature vessels in human uveal melanoma tumors and (2) to determine whether vessel maturation is associated with the major indicators for poor prognosis. Immunohistochemical analyses were performed on human tissue specimens from enucleated eyes (n = 14) to assess total vessels, neovessels, mature vessels, and cell proliferation. Tumor morphology was analyzed by hematoxylin and eosin and modified periodic acid-Schiff (PAS) staining.The spatial distribution of neovessels and mature vessels was analyzed by immunohistochemistry, and correlated with major indicators of poor prognosis (i.e., aggressive PAS patterns, epithelioid cytology, mitotic figures, extraocular extension, anterior tumor location, ciliary body involvement, large tumor size, cell proliferation, and angiogenic activity). Neovesseldensity was greater than mature vessel density in apical (p = 0.17), central (p = 0.036), and peripheral (p = 0.31) regions of the tumors, while mature vessel density was greater than neovessel density in basal areas of the tumor (p = 0.47). This pattern indicated that vessel maturation begins at the base of the tumor and later extends to the peripheral and apical regions. The difference between mature and neovessel densities for the apical (-0.8 +/- 1.9) and central areas (-0.8 +/- 1.3) of the tumor was significantly higher than the difference obtained for the basal area (0.3 +/- 1.6; p = 0.014 and p = 0.012, respectively), indicating a higher density of mature vessels compared to neovessels at the base. Statistical correlations were found between mature vessel density and tumor size (r = 0.48, p = 0.084), cell proliferation (r = 0.62, p = 0.042), and mitotic figures (r = 0.76, p = 0.001). Significant differences exist in the spatial distribution of mature versus neovessels in human uveal melanoma. Vessel maturation is associated with known clinical and pathologic indicators of poor prognosis (e.g., cell proliferation). Antiangiogenic therapy should be considered for the treatment of ocular malignancies; however, the results of this study indicate that blood vessel maturation heterogeneity may limit the efficacy of vessel targeting agents.Ophthalmic Research 04/2009; 41(3):160-9. · 1.56 Impact Factor
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ABSTRACT: Endoglin (CD105) is an accessory receptor of transforming growth factor B. The highest synthesis, as well as expression, of endoglin has been found in vascular endothelial cells. The involvement of endoglin in angiogenesis and in angiogenesis-dependent processes has been observed. Endoglin promotes angiogenesis not only by activation of vascular endothelial cell proliferation but also by induction of the antiapoptotic pathway in hypoxic endothelial cells. The potential application of endoglin as a tumour angiogenesis marker, useful for cancer diagnostics and clinical application, is anticipated. Endoglin expression may be useful as an indicator of disease progression and helpful for estimation of recurrence and metastasis risk.Contemporary Oncology / Wspólczesna Onkologia 01/2012; 16(1):68-71. · 0.21 Impact Factor